Sex differences in oxidant/antioxidant balance under a chronic mild stress regime

Abstract The deterioration of homeostasis between oxidant/antioxidant species may represent an important mechanism linking psychological stress to cardiovascular risk despite the many sex differences in stress responsiveness. The goal of the present study was to investigate the influence of chronic mild stress (CMS), a widely accepted animal model of depression, on oxidative homeostasis–allostasis markers and sICAM-1, a marker of endothelial injury, in the serum of Wistar rats, by taking into account the effect of sex. After six weeks of exposure to mild unpredictable environmental stressors, both male and female rat groups displayed typical changes in hedonic status (anhedonia), which is a core symptom of human depression. Control female rats had higher (nitrite and nitrate) NOx, lower malondealdehyde (MDA) levels with lower activity of antioxidant enzymes and sICAM-1 levels than did control males. CMS induced oxidant/antioxidant responses in both sexes. Females tended to increase their nitric oxide (NO) levels further, while MDA levels did not reach those of males, thus retaining significantly higher NO bioavailability than in males. Concerning the antioxidant enzymes, CMS-females exhibited significantly higher glutathione peroxidase (GPx) activity and lower glutathione reductase (GR) and superoxide dismutase (SOD) activity compared to CMS-males. The CMS response in females was accompanied by lower sICAM-1 levels than in males, suggesting lower endothelial injury. In conclusion, the results of the present study showed that CMS induces different oxidative stress and compensatory responses in both sexes probably due to differences in the mechanisms regulating oxidant/antioxidant pathways.